It is time for new male contraceptives!

The development of new male contraception began in the 1970s supported by government agencies in many countries including China (gossypol, no-scalpel vasectomy) (Li et al., 1991; Waites et al., 1998), India (reversible intravasal occlusion) (Guha et al., 1997), and the United States (hormonal male contraception) (Patanelli, 1978). Collaboration between the World Health Organization (WHO), United States National Institute of Child Health and Human Development, and other government and non-government organizations promoted male contraceptive development with many hormonal male contraception clinical trials (Waites, 2003). Led by the WHO in 1990s, two landmark studies provided evidence that if spermatogenesis is suppressed and sperm output is decreased to very low levels by exogenously administered testosterone, contraceptive efficacy of this male method is as effective as female hormonal methods (World Health Organization Task Force on Methods for the Regulation of Male Fertility, 1990; World Health Organization Task Force on the Regulation of Male Fertility, 1996). Since then, a number of studies confirmed that contraceptive efficacy comparable to female hormonal methods can be achieved with androgens alone or together with progestins (Gu et al., 2003; Turner et al., 2003). This included a multicenter male contraceptive study in China that recruited over 1000 couples who received injectable testosterone undecanoate (Gu et al., 2009). Moreover, analyses of recovery of spermatogenesis after withdrawal of the hormones confirmed that hormonal male contraception is reversible in most if not all men (Liu et al., 2006). Since then, the goal for researchers is to find combinations of androgens and progestins that are potent, user friendly, bioavailable as oral formulations or transdermal application and with least adverse events (Page et al., 2008; Nieschlag, 2013; Piotrowska et al., 2016; Wang et al., 2016). At the same time with the advance in the understanding of the molecular and cellular mechanisms of the regulation of spermatogenesis and sperm maturation, a number of promising non-hormonal targets are being investigated. These methods target a specific protein when inhibited by small molecules, or knocked out in mice will lead to infertility. Although these leads have enormous promise and preclinical studies are ongoing, clinical studies have not yet started (Tash et al., 2008; Chung et al., 2011; Matzuk et al., 2012; Paik et al., 2014; Zdrojewicz et al., 2015; O’Rand et al., 2016). The Male Contraceptive Summit meetings organized by Dr. Eberhard Nieschlag brought together academics, non-government organizations, government funding agencies, industry partners, provided recommendations for Regulatory Approval for Male Contraception based largely on expert opinions (Aaltonen et al., 2007). Although the pharmaceutical companies provided androgens and progestins for clinical trials, only two of them united to conduct a single placebo-controlled study. This study utilized a testosterone ester and a progestin implant that demonstrated the effectiveness of hormonal contraception and compared adverse events in the placebo versus treated groups (Piotrowska, et al., 2016). Although the study was very efficacious, the pharmaceutical industry changes through mergers and acquisitions led to changes in strategies and no further interest in development of male contraceptives. During these last 10 years, the development of male contraception is largely supported by the World Health Organization, Contraceptive Research and Development program, and the Population Council but the strongest and continuous support comes from the Contraceptive Research Branch of Eunice Kennedy Shriver National Institute of Child Health and Human Development. The NICHD is supporting male contraceptive clinical trials in new orally bioavailable androgens (Attardi et al., 2006; Surampudi et al., 2014) and a transdermal method (Ilani et al., 2012) in collaboration with the Population Council. The institute also supports research in identifying and developing new targets of male contraception. In 2013, Dr. David Serfaty, a founding member of the European Society of Contraception and Reproductive Health, together with Dr. Regine Sitruk Ware from the Population Council approached a number of academics and interested persons in government and non-government agencies and founded the International Consortium of Male Contraception (ICMC) (www.ic-mc.info). This consortium’s mission is to advocate for the advancement of male contraception and promote collaboration among investigators, government and non-government agencies, industry and interested groups. The ICMC sponsored sessions in 2014 and 2016 at the European Congress of Contraception and Reproductive Health generated interest among participants of these congresses, many of whom are gynecologists as well as family planning providers. In addition, the First International Congress on Male